Chapter 20 The ‘Untrammelled’ Scientist and the ‘Normal’ Volunteer: Some Reflections

Abstract Background Autism spectrum disorder is a condition related to brain development that affects a person’s perception and socialization, resulting in problems in social interaction and communication. It has no single known cause, yet several different genes appear to be involved in autism. As a genetically complex disease, dysregulation of miRNA expression and miRNA–mRNA interactions might be a feature of autism spectrum disorder. The aim of the current study was to investigate the expression profile of circulating miRNA-128, miRNA-7 and SHANK gene family in ASD patients and to assess the possible influence of miRNA-128 and miRNA-7 on SHANK genes, which might provide an insight into the pathogenic mechanisms of ASD and introduce noninvasive molecular biomarkers for the disease diagnosis and prognosis. Quantitative real-time PCR technique was employed to determine expression levels of miRNA-128, miRNA-7 and SHANK gene family in blood samples of 40 autistic cases along with 30 age- and sex-matched normal volunteer subjects. Results Our study revealed a statistical significant upregulation of miRNA-128 expression levels in ASD cases compared to controls (p value < 0.001). A statistical significant difference in SHANK-3 expression was encountered on comparing cases to controls (p value < 0.001). However, miRNA-7 expression showed no significant difference between the studied groups. Conclusions MiRNA-128 and SHANK-3 gene are emerging players in the field of ASD. They are promising candidates as noninvasive biomarkers in autism. Future studies are needed to emphasize their pivotal role.

Download Full-text

Alveolar macrophages from systemic sclerosis patients: evidence for IL-4-mediated phenotype changes

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00351.2003 ◽

2004 ◽

Vol 286 (6) ◽

pp. L1202-L1209 ◽

Cited By ~ 12

Author(s):

Raymond F. Hamilton ◽

Ed Parsley ◽

Andrij Holian

Keyword(s):

Systemic Sclerosis ◽

Alveolar Macrophages ◽

Lung Inflammation ◽

Costimulatory Molecule ◽

Normal Volunteer ◽

Macrophage Phenotype ◽

Histocompatibility Complex ◽

Ifn Γ ◽

Lung Lobes

The mechanism of chronic lung inflammation leading to lung fibrosis is unknown and does not have a characteristic inflammatory macrophage phenotype. This study was undertaken to determine whether a change in macrophage phenotype could account for chronic lung inflammation. In this study, human alveolar macrophages (AM) from subjects with systemic sclerosis (SSc) were obtained from bronchoalveolar lavage (BAL) and characterized on the basis of function (response to LPS), phenotype, and relative cell-surface B7 expression. AM from the subjects' disease-involved and noninvolved lung lobes were compared with each other and to AM from normal volunteer BAL. AM from involved SSc lobes produced significantly more interleukin (IL)-1β and PGE2 than AM from uninvolved lobes in response to LPS, but there was no spontaneous production of either mediator. The activator AM phenotype designated by RFD1+ surface epitope was significantly elevated in SSc BAL samples compared with normal BAL, although there were no differences comparing involved vs. noninvolved lobes within SSc subjects. The major histocompatibility complex II costimulatory molecule B7.2 was also significantly elevated in SSc AM compared with normal AM, again with no differences between involved and noninvolved lobes. In an attempt to determine environmental influences on AM phenotypes, normal AM were cultured in vitro with IFN-γ, IL-3, IL-4, IL-10, IL-12, or dexamethasone for 6 days. Of the cytokines examined, only IL-4 induced significant increases in both the activator phenotype RFD1+ and B7.2 expression. Taken together, these results indicate that IL-4 could account for proinflammatory AM phenotype changes and B7 surface-marker shifts, as seen in subjects with SSc.

Download Full-text

A unique protein in normal human cerebrospinal fluid.

Clinical Chemistry ◽

10.1093/clinchem/29.10.1842 ◽

1983 ◽

Vol 29 (10) ◽

pp. 1842-1844 ◽

Cited By ~ 4

Author(s):

N M Papadopoulos ◽

P A LeWitt ◽

R P Newman ◽

M I Raphaelson ◽

T N Chase

Keyword(s):

Cerebrospinal Fluid ◽

Serum Proteins ◽

Normal Volunteer ◽

Protein Band ◽

Serum Samples ◽

Immunofixation Electrophoresis ◽

Normal Human ◽

Monospecific Antibodies ◽

Immunoprecipitation Reaction ◽

Individual Human

Abstract On analysis of cerebrospinal fluid (CSF) samples from normal volunteer donors by high-resolution zone electrophoresis on agarose gel, an electrophoretically homogeneous protein band consistently appeared in the gamma-globulin region. Application of immunofixation electrophoresis in attempts to identify the band with use of monospecific antibodies against individual human serum proteins and against heavy- and light-chain immunoglobulins as well as polyvalent antisera did not produce a positive immunoprecipitation reaction with the protein band. The serum samples from these subjects did not show similar bands. Therefore, we conclude that this protein band is a normally occurring protein that is unique to CSF.

Download Full-text

Use of [11C]Aminocyclohexanecarboxylate for the Measurement of Amino Acid Uptake and Distribution Volume in Human Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1990.126 ◽

1990 ◽

Vol 10 (5) ◽

pp. 727-739 ◽

Cited By ~ 30

Author(s):

Robert A. Koeppe ◽

Thomas Mangner ◽

A. Lorris Betz ◽

Barry L. Shulkin ◽

Richard Allen ◽

...

Keyword(s):

Amino Acid ◽

Human Brain ◽

Amino Acid Transport ◽

Normal Volunteer ◽

Amino Acid Uptake ◽

Distribution Volume ◽

Transport Rate ◽

Acid Uptake ◽

Acid Transport ◽

Influx Rate

A quantitative positron emission tomographic (PET) method to measure amino acid blood–brain barrier (BBB) transport rate and tissue distribution volume (DV) has been developed using 11C-labeled aminocyclohexanecarboxylate (ACHC), a nonmetabolized amino acid analogue. Dynamic PET data were acquired as a series of 15 scans covering a total of 60 min and analyzed by means of a two-compartment, two-parameter model. Functional images were calculated for the amino acid transport rate constants across the BBB and the amino acid DV in the brain. Results show [11C]ACHC to have an influx rate constant in gray matter of ∼0.03–0.04 ml g−1 min−1, indicating a single-pass extraction fraction of ∼5–7%. The intersubject coefficient of variation was ∼15% while intrasubject variability of repeat scans was only slightly greater than 5%. Studies were performed in 15 young normal volunteer control subjects, 5 elderly controls, 7 patients with probable Alzheimer's disease, and one patient with phenylketonuria. Results indicate that [11C]-ACHC will serve as the basis of a method for measuring amino acid transport rate and DV in the normal and pathological human brain.

Download Full-text

On the psychometric properties of the Maudsley Marital Questionnaire (MMQ): Evaluation of self-ratings in distressed and ‘normal’ volunteer couples based on the dutch version

Personality and Individual Differences ◽

10.1016/0191-8869(83)90151-4 ◽

1983 ◽

Vol 4 (3) ◽

pp. 293-306 ◽

Cited By ~ 118

Author(s):

Willem A. Arrindell ◽

Willem Boelens ◽

Hein Lambert

Keyword(s):

Psychometric Properties ◽

Normal Volunteer ◽

Dutch Version

Download Full-text

Enhanced HDAC (Histone Deacetylase) Enzyme Activities in Blood CD 34 + Cells in Patients with Myeloid Metaplasia Myelofibrosis (MMM).

Blood ◽

10.1182/blood.v110.11.4657.4657 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4657-4657 ◽

Cited By ~ 2

Author(s):

Jen-Chin Wang ◽

Chi Chen ◽

Theresa Dumlao ◽

Thong Chang ◽

Yng-Li Xiao ◽

...

Keyword(s):

Histone Deacetylase ◽

Internal Control ◽

Target Genes ◽

Hdac Inhibitors ◽

Normal Volunteer ◽

Myeloproliferative Disorders ◽

Mrna Levels ◽

Myeloid Metaplasia ◽

Mutation Status ◽

Cd 34

Abstract We previously reported that histone deacetylase (HDAC) activity is elevated, but is not correlated to the JAK-2 mutation status, in patients with myelofibrosis myeloid metaplasia (MMM) (Blood 107:319b 2005). Now we have studied more patients: totally, 17 with MMM, 19 with other myeloproliferative disorders (MPD), and 16 normal volunteers as controls. Significantly elevated HDAC levels again was shown in patients with MMM compared with other MPD patients and normal volunteer controls (p<0.05). Sixteen patients with MMM were also studied for correlation between JAK-2 mutation status and HDAC levels; no significant correlation was found. We then studied which members of HDACs were elevated in patients with MMM. cDNA was prepared from total RNA obtained from blood CD 34+ cells; then QRT-PCR was performed using pre-made mixtures of primer and FAMTAMRA-labeled probes from ABI (www.appliedbiosystems.com). Primers and probe to GAPDH were used as internal controls. Cycle threshold (Ct) values were obtained graphically for target genes and internal control GAPDH gene products. Amplification efficiencies were calculated by plotting Ct s from serial diluted cDNAs for target genes and GAPDH and all with slopes below 0.1. Δ Ct values were obtained by subtracting GAPDH Ct from target gene Ct. Relative mRNA levels were determined by subtraction of normal control Δ Ct values from MMM Δ Ct values to give ΔΔ Ct values, which were converted to 2− ΔΔ Ct (Relative Quantitation of Gene Expression). The results showed elevated HDAC1 (2.80), HDAC2 (18.45), HDAC3 (2.10), HDAC 6 (2.03) HDAC 9 (2.71), SIRT3 (70.20), and SIRT6 (39.40) and depressed HDAC4 (0.01), HDAC5 (0.001), HDAC8 (0.001), SIRT2 (0.23), SIRT5 (0.005), and SIRT7 (0.88). () indicates relative mRNA values of MMM to controls. These results suggest that HDAC activities are elevated in patients with MMM and are elevated in many members of HDAC. This study may lay the basis for using HDAC inhibitors in clinical trials treating patients with MMM.

Download Full-text

Synergistic Effect of Ginger and Nifedipine on Human Platelet Aggregation: A Study in Hypertensive Patients and Normal Volunteers

The American Journal of Chinese Medicine ◽

10.1142/s0192415x06004089 ◽

2006 ◽

Vol 34 (04) ◽

pp. 545-551 ◽

Cited By ~ 26

Author(s):

Haw-Yaw Young ◽

Jung-Chun Liao ◽

Yuan-Shiun Chang ◽

Yen-Lin Luo ◽

Ming-Chin Lu ◽

...

Keyword(s):

Platelet Aggregation ◽

Synergistic Effect ◽

Normal Volunteer ◽

Hypertensive Patients ◽

Normal Volunteers ◽

Cerebrovascular Complication ◽

Aggregation Effect ◽

Human Platelet Aggregation ◽

Human Volunteers ◽

Normal Human

In this study, we evaluated the synergistic effect of ginger and nifedipine on anti-platelet aggregation in normal human volunteers and hypertensive patients. The results showed that the percentage of platelet aggregation induced by collagen, ADP and epinephrine in hypertensive patients was larger than that in normal volunteers. Either aspirin or ginger could potentiate the anti-platelet aggregation effect of nifedipine in normal volunteer and hypertensive patients. These results suggested that ginger and nifedipine possessed synergistic effect on anti-platelet aggregation. A combination of 1 g ginger with 10 mg nifedipine per day could be valuable for cardiovascular and cerebrovascular complication due to platelet aggregation.

Download Full-text

Bronchoalveolar Lavage in the Normal Volunteer Subject

CHEST Journal ◽

10.1378/chest.94.2.281 ◽

1988 ◽

Vol 94 (2) ◽

pp. 281-285 ◽

Cited By ~ 34

Author(s):

David B. Ettensohn ◽

Marilee J. Jankowski ◽

Andres A. Redondo ◽

Pamela G. Duncan

Keyword(s):

Bronchoalveolar Lavage ◽

Normal Volunteer ◽

Volunteer Subject

Download Full-text

Magnesium Reduces Calcium Oxalate Crystal Formation in Human Whole Urine

Clinical Science ◽

10.1042/cs0620017 ◽

1982 ◽

Vol 62 (1) ◽

pp. 17-19 ◽

Cited By ~ 38

Author(s):

P. C. Hallson ◽

G. A. Rose ◽

S. Sulaiman

Keyword(s):

Calcium Oxalate ◽

Inverse Correlation ◽

Normal Volunteer ◽

Urine Samples ◽

Magnesium Concentration ◽

Crystal Formation ◽

Calcium Oxalate Crystal ◽

Isotopic Methods ◽

Whole Urine

1. A low urinary magnesium was induced in normal volunteer subjects by giving cellulose phosphate; magnesium was added in vitro to yield urine samples of normal and high magnesium concentrations 2. After rapid evaporation of these urine samples at pH 5.3 to standard osmolality the calcium oxalate crystals were measured by microscopy and isotopic methods 3. There was a clear inverse correlation between magnesium concentration and calcium oxalate crystal formation 4. The case for treating calcium oxalate urolithiasis with magnesium is strengthened.

Download Full-text